Freed-amino acids in human cerebrospinal fluid of alzheimer disease, multiple sclerosis, and healthy control subjects

Fisher, G. H.; Petrucelli, Leonard; Gardner, C. E.; Emory, Carolyn; Frey, William H.; Amaducci, L.; Sorbi, Sandro; Sorrentino, Giovanna; Borghi, Mauro; D’Aniello, Antimo

doi:10.1007/bf02815405

Cited by 61 publications

(43 citation statements)

References 35 publications

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“…1,2 In addition to drug discovery, identifying the roll that L-and D-amino acids pay in protein structure [3][4][5][6] has challenged modern analytical methodology. Chiral modification of protein structure has been implicated in the formation of cataracts 7 the ageing process 8,9 , neurotransmission, endocrine regulation 10 , cancer 11 , Alzheimer's disease 12,13 , and multiple sclerosis 14 . Enantiomeric ratio have also been used to evaluate the quality of food material 15,16 , to determine the age of fossils and geological strata 17,18 and to search for extraterrestrial life 19,20 .…”

Section: Introductionmentioning

confidence: 99%

Gas-Phase Chiral Separations by Ion Mobility Spectrometry

et al. 2006

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This manuscript introduces the concept of Chiral Ion Mobility Spectrometry (CIMS) and presents examples demonstrating the gas phase separation of enantiomers of a wide range of racemates including pharmaceuticals, amino acids and carbohydrates. CIMS is similar to traditional ion mobility spectrometry (IMS), where gas phase ions, when subjected to a potential gradient are separated at atmospheric pressure due to differences in their shapes and sizes. In addition to size and shape, CIMS separates ions based on their stereospecific interaction with a chiral gas. In order to achieve chiral discrimination by CIMS, an asymmetric environment was provided by doping the drift gas with a volatile chiral reagent. In this study S-(+)-2-butanol was used as a chiral modifier to demonstrate enantiomeric separations of atenolol, serine, methionine, threonine, methyl-α-glucopyranoside, glucose, penicillamine, valinol, phenylalanine, and tryptophan from their respective racemic mixtures.

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Section: Introductionmentioning

confidence: 99%

Gas-Phase Chiral Separations by Ion Mobility Spectrometry

et al. 2006

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“…-Asp is localized in various neurons of rat brain, including the hippocampus, and in the hypothalamo-neurohypophyseal system suggesting its involvement in regulating the neurosecretory system (Schell et al 1997, D'Aniello et al 2000a, Wang et al 2000. In vertebrates, this amino acid occurs in the nervous tissues of chickens (Neidle & Dunlop 1990), rats (Dunlop et al 1986, D'Aniello et al 1993, 2000a,b, Hashimoto et al 1993 and humans (Fisher et al 1991(Fisher et al , 1994). An extremely high content of -Asp was detected in human brain (Fisher et al 1991) as well as in the cerebrospinal fluid (Fisher et al 1994).…”

Section: Introductionmentioning

confidence: 99%

“…In vertebrates, this amino acid occurs in the nervous tissues of chickens (Neidle & Dunlop 1990), rats (Dunlop et al 1986, D'Aniello et al 1993, 2000a,b, Hashimoto et al 1993 and humans (Fisher et al 1991(Fisher et al , 1994). An extremely high content of -Asp was detected in human brain (Fisher et al 1991) as well as in the cerebrospinal fluid (Fisher et al 1994). In addition, -Asp may participate in brain development, differentiation and functioning (Hashimoto et al 1993, Hashimoto & Oka, 1997, Sakai et al 1998a or may be a novel messenger in neuronal and neuroendocrine organs (Schell et al 1997.…”

Section: Introductionmentioning

confidence: 99%

“…In addition, -Asp may participate in brain development, differentiation and functioning (Hashimoto et al 1993, Hashimoto & Oka, 1997, Sakai et al 1998a or may be a novel messenger in neuronal and neuroendocrine organs (Schell et al 1997. Most recent investigations have examined the endocrine system of mammals where -Asp is well represented in the pineal gland (Imai et al 1995, Lee et al 1997, Takigawa et al 1998, hypothalamus (Fisher et al 1994, Wang et al 2002, pituitary (D'Aniello et al 2000a,b), adrenals (Hamase et al 1997, Lee et al 2001 and gonads (D'Aniello et al 1996, Sakai et al 1998b. Maximal content and transient emergence of -Asp in these tissues correspond to their morphological and functional maturation (Hashimoto et al 1993.…”

Section: Introductionmentioning

confidence: 99%

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Endocrine roles of d-aspartic acid in the testis of lizard Podarcis s. sicula

Raucci¹,

D’Aniello²,

Fiore³

2005

Journal of Endocrinology

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In the lizard Podarcis s. sicula, a substantial amount of -aspartate (-Asp) is endogenous to the testis and shows cyclic changes of activity connected with sex hormone profiles during the annual reproductive phases. Testicular -Asp content shows a direct correlation with testosterone titres and a reverse correlation with 17 -estradiol titres.In vivo experiments, consisting of i.p. injections of 2·0 µmol/g body weight of -Asp or other amino acids, in lizards collected during the three main phases of the reproductive cycle (pre-reproductive, reproductive and post-reproductive period), revealed that the testis can specifically take up and accumulate -Asp alone. Moreover, this amino acid influences the synthesis of testosterone and 17 -estradiol in all phases of the cycle. This phenomenon is particularly evident during the pre-and post-reproductive period, when endogenous testosterone levels observed in both testis and plasma were the lowest and 17 -estradiol concentrations were the highest. -Asp rapidly induces a fall in 17 -estradiol and a rise in testosterone at 3 h post-injection in the testis and at 6 h post-injection in the blood. In vitro experiments show that testicular tissue converted -Asp into -Asp through an aspartate racemase. -Asp synthesis was measured in all phases of the cycle, but was significantly higher during the reproductive period with a peak at pH 6·0. The exogenous -Asp also induces a significant increase in the mitotic activity of the testis at 3 h (P<0·05) and at 6 h (P<0·01). Induction of spermatogenesis by -Asp is recognized by an intense immunoreactivity of the germinal epithelium (spermatogonia and spermatids) for proliferation cell nuclear antigen (PCNA). The effects of -Asp on the testis appear to be specific since they were not seen in lizards injected with other -or -forms of amino acids with known excitatory effects on neurosecretion. Our results suggest a regulatory role for -Asp in the steroidogenesis and spermatogenesis of the testis of the lizard Podarcis s. sicula.

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“…Для дифференциации молекул Аb с физиологической конформацией (фАb) от молекул-частиц Аb с модифицированной конформацией введена аббревиатура "нано-Аb" для отличия этих двух продуктов b-процессинга АРР. Интрацеребральное отложение патологического нано-Аb [17,18], помимо БА, возможно при синдроме Дауна, врожденных церебральных гематомах с амилоидозом фамильной формы и нормальном старении [19]. Нано-Аb является нерастворимым фрагментом большого трансмембранного гликопротеина, или APP.…”

Section: этиология и патогенез болезни альцгеймераunclassified

Intensive protein synthesis in neurons and phosphorylation of beta-amyloid precursor protein and tau-protein are triggering factors of neuronal amyloidosis and Alzheimer's disease

et al. 2013

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Recently the studies of Alzheimer’s disease have become particularly actual and have attracted scientists from all over the world to this problem as a result of dissemination of this dangerous disorder. The reason for such pathogenesis is not known, but the final image, for the first time obtained on microscopic brain sections from patients with this disease more than a hundred years ago, is well known to clinicists. This is the deposition of Ab amyloid in the brain tissue of senile plaques and fibrils. Many authors suppose that the deposition of beta-amyloid provokes secondary neuronal changes which are the reason of neuron death. Other authors associate the death of neurons with hyperphosphorylation of tau-proteins which form neurofibrillar coils inside nerve cells and lead to their death. For creation of methods of preclinical diagnostics and effective treatment of Alzheimer’s disease novel knowledge is required on the nature of triggering factors of sporadic isoforms of Alzheimer’s disease, on cause-effect relationships of phosphorylation of amyloid precursor protein with formation of pathogenic beta-amyloids, on the relationship with these factors of hyperphosphorylation of tau-protein and neuron death. In this review we analyze the papers describing the increasing of intensity of biosynthesis in neurons in normal conditions and under the stress, the possibility of development of energetic unbalanced neurons and activation of their protective systems. Phosphorylation and hyperphosphorylation of tau-proteins is also tightly connected with protective mechanisms of cells and with processes of evacuation of phosphates, adenosine mono-phosphates and pyrophosphates from the region of protein synthesis. Upon long and high intensity of protein synthesis the protective mechanisms are overloaded and the complementarity of metabolitic processes is disturbed. This results in dysfunction of neurons, transport collapse, and neuron death.

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Freed-amino acids in human cerebrospinal fluid of alzheimer disease, multiple sclerosis, and healthy control subjects

Cited by 61 publications

References 35 publications

Gas-Phase Chiral Separations by Ion Mobility Spectrometry

Gas-Phase Chiral Separations by Ion Mobility Spectrometry

Endocrine roles of d-aspartic acid in the testis of lizard Podarcis s. sicula

Intensive protein synthesis in neurons and phosphorylation of beta-amyloid precursor protein and tau-protein are triggering factors of neuronal amyloidosis and Alzheimer's disease

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